Carisoprodol is a commonly prescribed centrally acting muscle relaxant that has high abuse potential. Much of its activity has been attributed to meprobamate, a major metabolite of carisoprodol. It is somewhat surprising that carisoprodol was synthesized 50 years ago; it has been extensively studied and, yet, it is not known whether carisoprodol itself has any central actions. In this issue, Gonzalez et al., describe a study to determine the activity of carisoprodol toward the GABAA receptors in light of the fact that meprobamate is structurally similar and is known to act centrally via these receptors. Activation of the GABAA receptor was examined with whole-cell patch-clamp experiments, and it was found that carisoprodol had a barbiturate-like agonist profile with antagonist activity at high concentrations. In the absence of GABA, it produced inward currents larger than those triggered by meprobamate. Carisprodol did not, however, show similar activity with ρ1 or glycine α1 receptors. The in vivo central GABAergic activity of carisoprodol was examined and found to be similar to meprobamate, a benzodiazepine, and barbiturate. Discrimination studies conducted with carisoprodol-trained rats showed that carisoprodol effects were antagonized by a barbiturate antagonist but not by a benzodiazepine antagonist. The study also identified functional traits associated with carisoprodol treatment that are likely to contribute to abuse potential, it suggests that the barbiturate activity of carisoprodol might not be solely due to the meprobamate metabolite.
See article at J Pharmacol Exp Ther 2009, 329:827-837.
- The American Society for Pharmacology and Experimental Therapeutics